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Pathogenic theory of schizophrenia
The pathogenic theory of schizophrenia, also called the germ theory of schizophrenia, is a pathogenic theory of disease in which it is thought that a proximal cause of certain cases of schizophrenia is the interaction of the developing fetus with pathogens such as viruses, or with antibodies from the mother created in response to these pathogens (in particular, Interleukin 8). Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES.(2004) Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry. 161(5):889-95. In the 1896 edition of his textbook, Emil Kraepelin suggested that dementia praecox might be caused by an infection of the bodily organs that caused autointoxication. Noll R.(2004) Historical review: autointoxication and focal infection theories of dementia praecox. World Journal of Biological Psychiatry volume 5, pages 66–72. Eugen Bleuler suggested that "... the connection of the disease schizophrenia to infectious processes equally needs further study." Bleuler E.(1911) Dementia Praecox, or the Group of chizophrenias.New York, NY: International Universities Press; pages 343–344. PMID 15121655 (free full text) Am. Psych. Assn. Abstract:"OBJECTIVE: Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines—interleukin-8 (IL-8), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-)—are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects. METHOD: The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959–1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1ß, IL-6, and TNF- were determined by sandwich enzyme-linked immunosorbent assay. RESULTS: The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1ß, IL-6, or TNF-. CONCLUSIONS: Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder." (Emphasis supplied.) Substantial research suggests that exposure to certain illnesses (e.g., influenza) in the mother of the neonate (especially at the end of the second trimester) causes defects in neural development which may emerge as a predisposition to schizophrenia around the time of puberty, as the brain grows and develops.Brown, Alan S. (Columbia University) Prenatal infection as a risk factor for schizophrenia Schizophrenia Bulletin, doi:10.1093/schbul/sbj052 (Oxford Univ. Feb. 2006) Abstract: "Accumulating evidence suggests that prenatal exposure to infection contributes to the etiology of schizophrenia. This line of investigation has been advanced by birth cohort studies that utilize prospectively acquired data from serologic assays for infectious and immune biomarkers. These investigations have provided further support for this hypothesis and permitted the investigation of new infectious pathogens in relation to schizophrenia risk. Prenatal infections that have been associated with schizophrenia include rubella, influenza, and toxoplasmosis. Maternal cytokines, including interleukin-8, are also significantly increased in pregnancies giving rise to schizophrenia cases. Although replication of these findings is required, this body of work may ultimately have important implications for the prevention of schizophrenia, the elaboration of pathogenic mechanisms in this disorder, and investigations of gene-environment interactions." Other researchers such as Yazar et al and Torrey et al have found a link between the Toxoplasma gondii organism and a heightened later risk of developing schizophrenia. They cite the known protozoa that cross the brain-body barrier and effect behaviour such as Plasmodium (malaria) and Trypanasoma (sleeping sickness) as evidence that such an infection could produce the behavioural changes associated with schizophrenia. A study by Joanne Webster confirmed that Haloperidol - often used in the treatment of schizophrenia - suppresses the effects of T. gondii and reverses its effect on the CNS of rats. However, it is not clear why Toxoplasma organisms can exist, albeit in small numbers, in the brains of apparently immune individuals and also why not all individuals infected with T. gondii do not go on to develop schizophrenia. Torry, E.F. & Yolken, R.H. (2007) 'Editors' Introduction: Schizophrenia and Toxoplasmosis' in Schizophrenia Bulletin, Vol 33, No 3, pp727-728 See also *Schizophrenia - link with influenza Notes Further reading *Munk-Jorgensen, Povl, Ewald, Henrik Epidemiology in neurobiological research: exemplified by the influenza—schizophrenia theory The British Journal of Psychiatry (2001) 178: s30-s32 ("In summary, the 10-year period of influenza—schizophrenia research in the 1980s and 1990s has provided strong inferential evidence that influenza infection in pregnancy, especially in the second trimester, can cause damage to the immature brain which increases the risk for schizophrenia later in life.") *McGrath J, Castle D. Does influenza cause schizophrenia? A five year review. Aust N Z J Psychiatry. 1995 Mar;29(1):23-31 ("There is a modest degree of consistency in support of an association between the 1957 influenza epidemic--and less so, for influenza epidemics in general--and later schizophrenia") *S. A. Mednick, R. A. Machon, M. O. Huttunen and D. Bonett (Univ. of So. Calif.) Adult schizophrenia following prenatal exposure to an influenza epidemic Arch. Gen. Psych Vol. 45 No. 2, February 1988 ("Those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia.") External links *Psychiatric News May 21, 2004 volume 39 number 10 Amer. Psych. Assn. Accessed 2007-01-15. ("Flu infection during early or middle pregnancy can sometimes lead to schizophrenia, blood taken from pregnant women and analyzed years later suggests.") *Reuters Health accessed 2007-01-15. ("Children born to women who contract the flu during pregnancy appear to have an increased risk for schizophrenia later in life, new research suggests. Prenatal influenza exposure may account for about 14 percent of schizophrenia cases, according to the findings presented here this week at the annual meeting of the American Psychiatric Association.")